Compounds for synthesizing steroids



Uni d Saw PM 1 2,786,837 COMPOUNDS FOR SYNTHESIZING STEROIDS Martin W. Farrar, Webster Groves, Harold Ralfelson, St.

Louis, and William S. Knowles, Kirkwood, Mo., assignors to Monsanto Chemical Company, St. Louis, Mo., a corporation of Delaware No Drawing. Original application July 23, 1953, Serial No. 369,944. Divided-and this application September 19, 1955, Serial No. 535,292

1 Claim. (Cl. 260-23955) This invention relates to methods and novel compounds of the icyclopentanodimethylpolyhydrophenanthrene series having a 3-keto group and adouble bond in the 4,5- position which compounds are intermediates in proceeding from a 17-formyl'cyclopent-16-eno-10,13-dimethyl- A -dccahydrophenanthren-3-0ne to a l7-(acyloxyacetyl)=17-hydroxywcyclopentano-10,13-din1ethyl- A dodecahydrophenanthren-Zi,1l-dione. In particular this invention relates to methods and novel compounds useful in the preparation of acyl derivatives .of 3,11,20-triketo- 17,2l-dihydroxy-A -pregnene from a 3-keto-17-formyl- A -androstatriene.

The sequence of .steps or series of reactions proceeding from a l7-formylecyclopent-l6-eno-10,13-dimethyl- A4901) decahydrophenanthrene-3-one to a 17-(acyloxy- CHO 2,786,837. Patented Mar. 26, 1957 acetyl)-17-hydroxycyclopentano-10,13-dimethyl A do decahydrophenantlrren-ESJl-dione essentially comprises (i) epoxidizing a l7-formyhcyclopent-l6-eno-l0,13-dimethyl-A -decahydrophenanthren-3-one with an oxygen furnishing agent, (2) convertingthe formyl group of ICC the 16,17-0Xido compound so formed to a-carboxyl group,

(3) reacting the carboxylic acid so obtained with an acyl halide forming agent, (4) reacting the resultant acid halide with 'diazomethane, (5) reacting the diazo-ketone soforme'cl with a carboxylic acid to form a 17-(acy1oxyacetyl)-16,17-oxido-cyclopentano-l0,13-dimethyl- A tdecahydrophenanthren-3one, (6) reacting said latter compound with a hydrogen halide, (7) reacting-the 16- halo-17-hydroxy-17-(acyloxyacetyl)-cyclopentano 10,13- dimetlryl-A -decahydrophenanthren-3-one so formed with a hypohalous acid, (8) oxidizing the 9,16-dihalo- 11, 17-dihydroxy-17- acyloxyacetyl) -cyclopentano-l0, 13 dimethyl-M-dodecahydrophenanthren-3-one with a compleX of chromium oxide and a tertiary amine, (9) dehalogenating the 9,16-dihalo-17-h ydroxy-17 (acyloxyacetyl)-cyclopentano-l0,13-dimethyl A dodecahydrophenanthren-3,11-dionc so as to produce a 17-(acyloxyacetyl)-17-hydr0xy-cyc1opentano 10,13 dimethyl-M dodecahydrophenanthren-S,1l-dione. The aforesaid sequence of steps is outlined schematically asfollowsz CHO 00011 1? i ii? .hydrophenanthren-la-one together in an organic medium which is non-reactive under the reaction conditions. Suitable media include chloroform, carbon tetrachloride, diethyl ether, glacial acetic acid, methanol, ethanol, isopropanol, and the like. The temperature employed in the epoxidation may vary widely but ordinarily will be in the range of from about -10 C. to about 50 C. A con venient reaction medium when the oxidant is hydrogen peroxide is a low molecular weight alcohol.

As illustrative of the first step of the process of this invention is the following:

EXAMPLE I To a suitable reaction vessel containing 50 parts by weight (substantially 0.169 mol) of dl-3-keto-17-formyl- A -androstatriene (M. P. 178-1785 .C.) dissolved in 4200 parts by weight of methanol maintained at about C. is added approximately 170 parts by weight of sodium carbonate as a 5% aqueous solution followed by a methanol-hydrogen peroxide mix containing approximately 5.7 parts by weight of hydrogen peroxide. The mix so obtained is stirred for about 16 hours at about 0 C. Thereupon substantially all of the methanol is removed by vacuum distillation and the residue is then taken up with chloroform. The chloroform solution is then washed with water and dried over anhydrous magnesium sulfate. Upon evaporation of the chloroform there is obtained a white solid residue, which upon triturating with diethyl ether yields white crystalline dl-3-ket0-16,17-oxido-17- formyl-A -androstadiene.

Similarly the individual optically active isomers such as the natural modification of 3-keto-l6,17-oxido-17-formyl- A -androstadiene are obtained beginning with the appropriate optically active isomer of 3-keto-17-formyl- A -androstatriene. The natural modification of 3- keto-16,17-oxido-17-formyl-A -androstadiene is obtained employing the procedure of Example I but replacing dl-3-keto-17-formyl-A randrostatriene with the dextro-rotatory form of 3-keto-17-formyl-A -androstratriene (melting point 160.5-161.5 C.).

The next step in the process of this invention is the conversion of the formyl group, i. e. the substituent in the 17-position, to a carboxy group (Compound III of the schematic diagram). This is readily brought about employing a mild oxidizing agent such as silver oxide, sodium chromate in acetic acid, and the like. As illustrative of the preparation of a 3-keto-16,17-oxido-17-carboxy-A -androstadiene is the following:

EXAMPLE II then filtered. The collected residue is washed with water and the washings, combined with the original filtrate.

The aqueous layer is acidified and then extracted with chloroform. The chloroform extracts are combined, dried and subjected to vacuum distillation. Upon evaporation of the chloroform there is obtained a solid residue which upon triturating with diethyl ether yields 35 parts by weight of crystalline dl-3-keto-l6,17-oxido-17-carboxy- A -androstadiene.

Similarly the individual optically active isomers such as the natural modification of 3-keto-16,17-oxido-17-carb0xy-A androstadiene are obtained beginning with the appropriate optically active isomer of 3-keto-l6,17-oxidol7-formyl-A -androstadiene.

The next step in the process of this invention the carboxylic acid (Compound III) is converted to its acid halide (Compound IV) employing an acyl halide forming agent such as oxalyl chloride and the like. As illustrative of the preparation of the acid halide (Compound IV) is the following:

EXAMPLE III To a solution containing approximately 50 parts by weight of dl-3-keto-16,l7-oxido-17-carboxy-A -androstadiene in approximately 4000 parts by weight of anhydrous methanol is added sufficient sodium methylate to neutralize the epoxy acid. The methanol is removed by vacuum distillation and to the residue is added and intimately mixed about 450 parts by weight of benzene and about 2.5 parts by weight of pyridine followed by about 250 parts by weight of oxalyl chloride while maintaining the temperature at about 10 C. The mix so obtained is allowed to stand for about 30 minutes, whereupon the mix is subjected to vacuum distillation while maintaining the temperature at about 15 C. The residue is then taken up with about 500 parts by weight of benzene and again subjected to vacuum distillation at about 15 C. The residue is taken up with about 250 parts by weight of benzene and filtered. Upon subjecting the filtrate to vacuum distillation there is obtained the solid acid chloride of al-3-keto-16,17-oxid0-17-carb0xy-A -androstadiene.

Similarly the individual optically active isomers such as the acid chloride of the natural modification of 3-keto- 16,17-0xid0-17-ca1'b0Xy-A -andr0stadiene are obtained from the appropriate optically active isomer.

The next step in the process of this invention is the preparation of the diazoketone (Compound V) by reacting diazomethane with an acid halide of a 16,17-oxido-17- carboXy-cyclopentano 10,13 dimethy1-A -decahydrophenanthren-3-one. Ordinarily an excess of two chemical equivalents of diazomethane is employed in converting the acid halide (Compound IV) to the diazoketone (Compound V) and in general the process is carried out in an inert organic solvent such as diethyl ether, benzene, dioxane, toluene, etc., at a temperature in the range of 20 to 40 C. As illustrative of the preparation of the diazoketone is the following:

EXAMPLE IV To a suitable reaction vessel containing an ether solution containing parts by Weight of diazomethane is added approximately 50 parts by weight of the acid chloride of dl-3 -keto-l6,17-oxido-17-carboxy-A -androstadiene dissolved in 500 parts by Weight of benzene while maintaining the temperature at about 0 C. The mixture so obtained is then agitated for about one hour at about 0 C. The mix is then subjected to vacuum distillation to remove the solvents whereupon there is obtained yellow crystalline dl-3,20-diketo-16,17-oxido-2ldiazo-A -pregnadiene.

Similarly the individual optically active isomers such as the natural modification of 3,20-diketo-16,17-oxido-21- diam-A -pregnadiene are obtained beginning with the acid halide of the appropriate optically active isomer of 3-keto-16,17-oxido-17-carboxy-A -androstadiene.

The next step in the process of this invention is the formation of the 17-(acyloxyacetyl)-l6,l7-oxido-cyclo- PQIHQQQ 3 dimethyl-A -decahydrophenanthren- 3-one (Comp-oundVI) from the diazoketone (Compound 'V) *by heat-ing the latter in the presence of a monocar- EXAMPLE V 'To a suitable reaction vessel containing approximately 5000 parts by weightof acetic acid is added approximately 50 parts by weight of dl-3,20-diketo-16,17-oxido-21-diazo- A -pregnadiene and themix so obtained heated at about 90-95 C. .for about .30 minutes. The resultant mix is then subjected to vacuum distillation and the residue .so obtained taken up with chloroform. The chloroform solution is .then Washed with aqueous sodium bicarbonate, then with water and finally dried. Upon removal of the solvent there is obtained solid dl-3,20-diketo-16,17-oxido- 21-acetyloxy-A -pregnadiene in .the form of white crystals.

Similarly the individual optically active isomers such as the natural modification of 3.,20-diketo-l6,17-oxido-2lacetyloxy-A -pregnadiene are obtained from the appropriate optically active isomer of 3,20-diketo-16,17- oxido-Z1-diazo-A -pregnadiene.

The next step of the process of this invention is the opening of the epoxide grouping by reacting the l7-(acyloxyacetyl) 16,17 oxido cyclopentano-10,13-dimethyl- A -decahydrophenanthren 3 one (Compound VI) with a hydrogen halide such as HCl, HBr or HI which results in the formation of a halo-hydrin (Compound VII), namely 16-halo-17-hydroxy 17 (acyloxyacetyl)- cyclopentano 10,13 dirnethyl-A -decahydrophenanthren-3-one. This reaction is preferably carried out in an inert organic solvent containing dissolved therein the hydrogen halide reactant and at a temperature in the range of about 20 C. to about 40 C. As illustrative of this step is the following:

EXAMPLE VI Approximately 40 pants by weight ofail-2i,20 diketo--1-6, 17-oxido-2l-acetyloxy-A Q -pregnadiene is admixed with approximately 3000 parts by weight of acetic acid and approximately 1000 parts by weight of benzene in a suitable reaction vessel. T hereto is added-while maintaining the temperature at about C. approximately 80 parts .byweight of a 38% acetic acidsolution of'ihydrogen bromide and the mix so obtained agitated for about 30 minutes at about 0 C. To the mix is then added an equal volume of water and the composite so obtained extracted with several small portions of chloroform. The chloroform extracts are combined, washed with water and dried over anhydrous magnesium sulfate. Upon subjecting the .so dried solution to vacuum distillation in order to remove the chloroform there is obtained White crystalline dl-3,20-diketo-l6fl bromo-17u hydroxy 21- acetyloxy-A -pregnadiene.

In a similar fashion but employing hydrogen chloride instead of hydro-gen bromide white crystalline a l-3,20- diketo-l 6B-chloro-l7a hydroxy 21-acetyloxy A pregnadiene is obtained from dl-3,20-'diketm16,17-oxide- 21-acetyloxy-A -pregnadiene.

Similarly the individual optically active isomers such as the natural modification of 3,20-diketo-16fl-bromo-l7uhydroxy 21 acetyloxy-A -pregnadiene are obtained from the appropriate optically active isomer of 3,20- diketo- 16,17-oxido-21aacetyloxy-n' -pregnadiene.

The next step in the process of this invention is the reacting of the 16-halo-17-hydroxy compound (Compound VII) with a hypohalous acid to form the 9,16-dihalo-1l,17-dihydroxy-17-(acyloxyacetyl) cyclopentano- .pound VIII).

. '6 10,13,dimethylen -dodecahydrophenanthrem3-0ne (Com- The addition reaction is brought about by mixing a solution of .a liypohalous acid, preferably hypobromous acid, with a solution of a 16 halo-17-hydroxy-17-(acyloxyacetyl)-cyclopentano-10,l3 dimethyl- A -decahydrophenanthren-3-one at a temperature in the range-of about 0 to 30 C. The 9-halo and ll-hydroxy substituents so introduced bear a transrelationship to one another, that'is one occupies the .plane above ring C while the other occupies the plane below ring C, however, it is to be understood that the element of this invention is not limited to any assumption as to chemical structure but pertains broadly to the 9-halo-1l-hydroxy addition product of a .hypohalous acid and a l6-halo-17- 'hydroxy-17-(acyloxyacetyl) cyclopentano 10,13 dimethyl-M -decahydrophenanthren-3-one (Compound VII). Various solvents which are inert under conditions of the addition reaction may be used in the preparation of the -9-hal0-l1-hydroxy addition product (Compound VIII), for example acetone, methyl ethyl ketone, methyl acetate, ethyl acetate, tert. butanol, etc.

In this step of the ,process of this invention it is preferred that the hypohalous acid employed be hypobromous acid and such can be prepared in several ways, for example by mixing mercuric oxide with bromine and Water and filtering off the mercuric bromide thus formed, or by mixing N-bromoacetamide with water and tertiary butanol or, preferably, by mixing a solution of N-bromo-succinimide CHzC in a suitable inert organic solvent, e. g. acetone, tertiary butanol, with water and a small amount of sulfuric acid. Where desired, the hypo'bromous acid solution can be prepared first and then mixed with 16 ha1o-17-hydroxy- 17-(acyloxyacetyl)-cyclopentano-10,13-dimethyl A decahydrophenanthren-3-one .(Compound -VII') or, preferably, the hypobromous acid is prepared in the presence of the reactant .(i. e. Compound VII) so that the elements of hypobromous acid add to the 9-11 double bond as soon as .they are formed. As illustrative of-this step of the process of this invention employing hypobromous acid is the following:

EXAMPLE VII To an agitating solution containing substantially 63 parts by weight of dl-3,20-diketo-l6 3-bromo-l7a-hydroxy- 21 acetyloxy-A -pregnadiene, substantially 2800 parts by weight of acetone and substantially 1200 parts by weight of water is added at about 0-5 C. approximately 50 parts by weight of l N sulfuric acid. To the so cooled and acidified solution is slowly added a solution con- .taining substantially 35 parts by weight of N-bromo-succinimide in approximately 360 parts by weight of acetone. Upon completion of the N-bromo-succim'mide addition the mix is agitated for about 5 hours at about 0-5 C., the bromohydrin crystallizes from the solution during the agitation. At the end of the agitation period aqueous sodium sulfite is added to destroy the excess N-bromosuccinimide and then the mix is neutralized with sodium bicarbonate. The mix is then filtered and the residue washed first with water, then with acetone and dried. The white crystalline-product so obtained is dl-3,20-diketo- 9a,l7fl-dibromo-11fl,l7a-dihydroxy 21 acetyloxy A pregnene.

In a similar fashion beginning :with dl-3,20-diketo-l6fl chloro-l'la-hydroxy-Zl-acetyloxy A pregnadiene white crystalline til-3,20-diketo-9a-bromo 1fifi-chloro-11,3, 17a-dihydroxy-2l-acetyloxy-A -pregnene is obtained.

=dl-3,20-.dlk6tO-9.06 ,'16B -.dichloro -11fl,17oa dihydroxy- 2l-acetyloxy-A -pregnene may be prepared by admixing the 9a-bromo-11/3hydroxy compound (i. e. the product 16/3-dibromo-1 1p,17a-dihydroxy-21-acetyloxy-A pregene are obtained from the appropriate optically active 3,20-

diketo-16,8-halo-17oe hydroxy 21 acetyloxy A pregnadiene. Y

The next step in the process of this invention is the oxidation of the ll-hydroxy substituent of Compound VIII of the foregoing schematic diagram to produce the 16- halo-17-hydroxy- 17- acyloxyacetyl) -:cyclopentano-9-h alo- 10,13-dimethyl-A -dodecahydrophenanthren 3,11 dione (Compound IX) Halogen EXAMPLE VIII To an agitated complex of chromium trioxide and pyridine prepared in the cold by admixing 50 parts by weight of chromium trioxide with 500 parts by weight of pyridine is added substantially 50 parts by weight of dl-3,20-diketo- 9,16-dibromo-l1,8,17a-dihydroxy 21 acetyloxy-A -pregnene in approximately 800 parts by weight of pyridine while maintaining the temperature at about C. The mixture so obtained is permitted to stand at room temperature for about 16 hours with occasional agitation. The mixture is then filtered and the residue Washed with pyridine. The pyridine wash and the original filtrate are combined and the solution so formed is poured into five times its Weight of water and the composite extracted with chloroform. The extracts are combined and cooled to about 0 C. The cooled solution is then washed with dilute hydrochloric acid and then with water. The organic layer is recovered, dried, and evaporated to dryness. The residue is white crystalline dl-3,11,20-tIlk6t0-90t,16|3-dlbromo-l7a-hydroxy-2l-acetyloxy-M-pregnene.

Replacing dl3,20-diketo-9a, 16,8-dibromo-1 1B,17u-'dihydroxy-2l-acetyloxy-A pregnene in Example VIII with an equal weight 'of dl-3,20-diketo-9a,16p-dichloro-11,3,17adihydroxy-2l-acetyloxy-A -pregnene and subjecting same to the series of steps set forth in Example VIII all-3,11,20- triketo-9a,165-dichloro-l7a-hydroxy 21 acetyloxy-A pregnene is obtained.

In a similar fashion the individual optically active isomers of 3,11,20-triketo-9a,16B-dihalo-17a-hydroxy-21- acetyloxy-A -pregnene, e. g. the natural modification of 3,11,20-triketo-9oz,16/3-dibromo 17a hydroxy-Zl-acetyloxy-A -pregnene is obtained from the appropriate optically active 3,20-diketo-9a,lop-dihalo 113,17u dihydroxy-Zlacetyloxy A -pregnene.

' 'lhe next step in the process of this invention is the filtered and the residue washed with warm acetone.

'droxy-2 l-acetyloxy-A -pregnene.

removal of the 9-halogen and 16-halogen substituents of the 16-halo 17 hydroxy 17- (acyloxyacetyl)-cyclopentano-9-halo 10,13 dimethyl-A -dodecahydrophenanthren-3,1l-dione. In this step the halogen substituent in the 9-position is removed first to provide a 16-halo-17- hydroxy l7 (acyloxyacetyl) cyclopentano-10,13-dimethyl-A -d0decahydr0phenanthren 3,11 dione (Compound X) which compound upon dehalogenating produces a 17 hydroxy 17 (acyloxyacetyl)-cyclopentano-10,13- dimethyl-A -dodecahydrophenanthren-3,ll-dione (Compound XI). It is preferred to remove both halogen substituents in one operation and as illustrative of this employing a large excess of Raney nickel is the following:

EXAMPLE IX To a suitable reaction vessel containing 20 parts by weight of Raney nickel, approximately 200 parts by weight of acetone and about 20 parts by weight of water is added approximately 3.5 parts by weight of dl-3,11,20-triketo- 9a,l6,8-dibromo-17othydroxy-21-acetyloxy A pregnene and the mixture so obtained refluxed in an atmosphere of nitrogen for about 4 hours. The reaction mix is then The washings and original filtrate are combined and subjected to vacuum distillation. The residue is then taken up with chloroform and the solution so formed washed with water and dried. The dried solution is then subjected to vacuum distillation whereupon there is obtained white crystalline dl-3,l1,20-triketo 17a hydroxy-Zl-acetyloxy A pregnene (M. P. 240243 C.) which compound is identical with the acetate of racernic (dl) cortisone.

Similarly the individual optically active isomers such 'as the natural modification (dextro rotatory form) of 3,11,ZO-triketo-Nix-hydroxy 21 acetyloxy-M-pregnene are obtained beginning with the appropriate optically active isomers of 3,11,20-triketo-9a,16p-dibromo-17a-hy- The 21-acyl derivative of the natural modification of 3,l1,20-triketo-17a,21-dihydroxy-A -pregnene according to infrared spectrum, melting point and optical rotation is identical with the corresponding acyl derivative of natural cortisone. Thusly, it is to be understood that the optically active isomers referred to hereinbefore as the natural modification'are those which through the course of reactions as afore schematically outlined starting with the dextro-rotatory form of 3-keto-17-formyl-A -androstatriene provide for the acyl derivatives of natural cortisone.

While as aforedescribed the 16 halo 17 hydroxy- 17 (acyloxyacetyl) cyclopentano 10,13 dimethyl- A -decahydrophenanthren-3-one compound (Compound VII) was employed to prepare the 9-halo-11-hydroxy addition product (Compound VIII) it has been found that it (i. e. Compound VII) upon dehalogenating provides. for a 17-hydroxy-17-(acyloxyacetyl)-cyclopentano 10,13 dimethyl A4301) decahydrophenanthren- 3-one which compound upon reacting with a hypohalous acid produces a 9-halo-11-hydroxy addition product which addition product upon dehalogenating yields a 11,17-dihydroxy 17 acyloxyacetyl) cyclopentano 10,13- dimethyl-A -dodecahydrophenanthren-3-one. This sequence of steps is outlined schematically as follows, R and x having the same significance as aforedescn'bed.

dru sonion onion 1 1 -on --on x Cl i 0= XIV XIII As illustrative these steps proceeding from Compound VII to Compounds XII and XIII and finally to Com-- pound XIV is the following:

EXAMPLE X To a suitable reaction vessel containing parts by weight of Raney nickel, approximately 100 parts by weight of acetone and about 10 parts by weight of water is added and intimately mixed 3 parts by weight of dl- 3,20 diketo 16,8 bromo 1701. hydroxy 21 acetyloxy-A -pregnadiene and the mixture so obtained refluxed in an atmosphere of nitrogen for about 4 hours. The reaction mix is then filtered and the residue washed with warm acetone. The washings and original filtrate are combined and subjected to vacuum distillation. The residue is then taken up with chloroform and the solution so formed washed with water and dried. The dried solution is then subjected to vacuum distillation Whereupon there is obtained white crystalline dl-3,20-diketo- 1 7a-hydroxy-2 1 -a.cetyloXy-A (11 -pregnadiene.

Similarly the individual optically active isomers such as the natural modification of 3,20-diketo17a-hydroxy- 2l-acetyloxy-M- -pregnadiene are obtained beginning with the appropriate optically active isomer of 3,20-diketo- 16 3 bromo 17cc hydroxy 21 acetyloxy A pregnadiene. The natural modification of dextro-rotatory form of 3,20-diketo-17a-hydroxy-21-acety1oxy-A pregnadiene possesses a melting point of 233-236 C.

The aforedescribed dl 3,20 diketo-17a-hydroxy-21- acetyloxy-A -pregnadiene upon reacting with a hypohalous acid such as hypobromous acid in accordance with the process of Example VII produces White crystalline dl 3,20 diketo 9a bromo 115,170: dihydroxy 21- acetyloxy-n' -pregnene which 9-bromo-11-hydroxy addition product upon dehalogenating using Raney nickel provides for dl-3,20-diketo-113,17a-dihydroxy-2l-acetyloxy- M-pregnene which compound has the same infrared spectrum as the (21-) acetate of 17-hydroxy corticosterone. Similarly but beginning with the natural modification of 3,20 diketo 17a hydroxy 21 acetyloxy 41 pregnadiene the acetate obtained is identical with the (21-) acetate of 17-hydroxy corticosterone.

The natural modification of 3-keto-l6,17-oxido-17- formyl-A -androstadiene referred to on page 5, lines 17ff, is a white crystalline substance melting at 193-197" C. The natural modification of 3-keto-16,17-oxido-17 carboxy-A -andr0stadiene referred to on page 7, lines lff, is a white crystalline substance melting at 211-212 C. The natural modification of 3,20-diketo-l6,17-oxido- 21-diazo-A -pregnadiene referred to on page 9, lines Sff, is a yellow crystalline substance melting at l168 C. The natural modification of 3,20-diketo-16fi-bromo- 17a-hydroxy-2l-acetyloxy-A -pregnadiene referred to on page 11, lines 1677, is a white crystalline substance melting at 146-148 C.

While this invention has been described with respect to certain embodiments it is not so limited and it is to be understood that variations and modifications thereof obvious to those skilled in the art may be made without departing from the spirit or scope of this invention.

This application is a division of our co-pending application Serial No. 369,944, filed July 23, 1953.

What is claimed is:

16,17 oxido 17 formyl cyclopentano 10,13 dimethyl-A -decahydrophenanthren-3-one CEO I U at] No references cited. 

1.,17 - OXIDO - 17 - FORMYL - CYCLOPENTANO - 10,13 - DIMETHYL-$4,9(11)-DECAHYDROPHENANTHREN-3-ONE 